: The inhibitory (GABAergic) neurons of the thalamic reticular nucleus (TRN) in mammals are located at the interface of the thalamocortical and corticothalamic pathways, from which they receive synaptic inputs. In turn, the TRN projects back to dorsal thalamic nuclei. Thus, the TRN is in a strategic position to influence thalamocortical interactions. There is some knowledge of the role of TRN during sleep, where it participates in the generation of spindles. However, the role of TRN in waking is unknown. In a recent study (Montero '97) combining a behavioral paradigm in which rats are naturally paying attention to the environment (exploration of a novel, complex environment) and a marker of neuronal activity (induction of the immediate-early gene c-fos), a remarkable result was noted: in normal exploring rats there is a selective activation of the visual segment of the TRN, located in caudodorsal part of the nucleus. By contrast, in blind exploring rats, which depend critically on tactile clues for recognition of the environment, there is instead a selective activation of the somatic segment of TRN, located in central part of the nucleus. In control awake, non-exploring rats there is no apparent activation of TRN. To explain these results, the following hypothesis is formulated: a) In the alert behaving animal, different sensory sectors of TRN are activated depending on the prevalent or essential sensory cues used for recognition of the environment; b) this activation optimizes thalamocortical transmission by increasing the inhibitory surround of the receptive fields of thalamic relay neurons; and, c) the selective activation of TRN sectors is under the command of the cortex with participation of excitatory inputs to TRN from the locus coeruleus. To test this hypothesis, in the proposed experiments, the following will be determined. 1) Specific Aim 1: whether the activation or inactivation of the visual TRN by glutamate or GABA iontophoresis, respectively, increases or decreases the inhibitory surround of receptive fields in the rat dorsal lateral geniculate nucleus. 2) Specific Aims 2-4: whether unilateral neurotoxic lesions restricted to locus coeruleus, or to corticoreticular neurons in layer 6 of the primary and extrastriate visual cortex, decrease the activation (detected by Fos-labeling) of the ipsilateral visual TRN in exploring rats. The results will advance our understanding of the role of TRN in the awake behaving animal, in particular with respect to its role in modulating thalamocortical transmission and in subcortical mechanisms of selective attention.